Skip to main content

Advertisement

Log in

Fluorescence guided surgery for pituitary adenomas

  • Topic Review
  • Published:
Journal of Neuro-Oncology Aims and scope Submit manuscript

Abstract

Purpose

Resection of pituitary adenomas presents a number of unique challenges in neuro-oncology. The proximity of these lesions to key vascular and endocrine structures as well as the need to interpret neuronavigation in the context of shifting tumor position increases the complexity of the operation. More recently, substantial advances in fluorescence-guided surgery have been demonstrated to facilitate the identification of numerous tumor types and result in increased rates of complete resection and overall survival.

Methods

A review of the literature was performed, and data regarding the mechanism of the fluorescence agents, their administration, and intraoperative tumor visualization were extracted. Both in vitro and in vivo studies were assessed. The application of these agents to pituitary tumors, their advantages and limitations, as well as future directions are presented here.

Results

Numerous laboratory and clinical studies have described the use of 5-ALA, fluorescein, indocyanine green, and OTL38 in pituitary lesions. All of these drugs have been demonstrated to accumulate in tumor cells. Several studies have reported the successful use of the majority of the agents in inducing intraoperative tumor fluorescence. However, their sensitivity and specificity varies across the literature and between functioning and non-functioning adenomas.

Conclusions

At present, numerous studies have shown the feasibility and safety of these agents for pituitary adenomas. However, further research is needed to assess the applicability of fluorescence-guided surgery across different tumor subtypes as well as explore the relationship between their use and postoperative clinical outcomes.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

(with permission from Hadjipanayis et al. [25])

Fig. 2

(with permission from Cho et al. [28])

Fig. 3

(with permission from Cho et al. [28])

Fig. 4

(with permission from Falco et al. [35]

Similar content being viewed by others

References

  1. Ezzat S, Asa SL, Couldwell WT et al (2004) The prevalence of pituitary adenomas: a systematic review. Cancer 101:613–619. https://doi.org/10.1002/cncr.20412

    Article  PubMed  Google Scholar 

  2. Freda PU, Wardlaw SL (1999) Diagnosis and treatment of pituitary tumors. J Clin Endocrinol Metab 84:3859–3866. https://doi.org/10.1210/jcem.84.11.6202

    Article  CAS  PubMed  Google Scholar 

  3. Salomon MP, Wang X, Marzese DM et al (2018) The epigenomic landscape of pituitary adenomas reveals specific alterations and differentiates among acromegaly, cushing’s disease and endocrine-inactive subtypes. Clin Cancer Res 24:4126–4136. https://doi.org/10.1158/1078-0432.CCR-17-2206

    Article  CAS  PubMed  Google Scholar 

  4. Brucker-Davis F, Oldfield EH, Skarulis MC et al (1999) Thyrotropin-secreting pituitary tumors: diagnostic criteria, thyroid hormone sensitivity, and treatment outcome in 25 patients followed at the National Institutes of Health. J Clin Endocrinol Metab 84:476–486. https://doi.org/10.1210/jcem.84.2.5505

    Article  CAS  PubMed  Google Scholar 

  5. Ntali G, Capatina C, Grossman A, Karavitaki N (2014) Functioning gonadotroph adenomas. J Clin Endocrinol Metab 99:4423–4433. https://doi.org/10.1210/jc.2014-2362

    Article  CAS  PubMed  Google Scholar 

  6. Sharma MD, Nguyen AV, Brown S, Robbins RJ (2017) Cardiovascular disease in acromegaly. Methodist DeBakey Cardiovasc J 13:64–67. https://doi.org/10.14797/mdcj-13-2-64

    Article  PubMed  PubMed Central  Google Scholar 

  7. Ferrau F, Korbonits M (2015) Metabolic comorbidities in Cushing’s syndrome. Eur J Endocrinol 173(4):M133–M157

    Article  CAS  Google Scholar 

  8. Esposito D, Olsson DS, Ragnarsson O et al (2019) Non-functioning pituitary adenomas: indications for pituitary surgery and post-surgical management. Pituitary 22:422–434. https://doi.org/10.1007/s11102-019-00960-0

    Article  PubMed  PubMed Central  Google Scholar 

  9. Jho H-D AA (2000) Endoscopic transsphenoidal pituitary surgery: various surgical techniques and recommended steps for procedural transition. Br J Neurosurg 14:432–440. https://doi.org/10.1080/02688690050175229

    Article  CAS  PubMed  Google Scholar 

  10. Jho H-D, Carrau RL (1997) Endoscopic endonasal transsphenoidal surgery: experience with 50 patients. J Neurosurg 87:44–51. https://doi.org/10.3171/jns.1997.87.1.0044

    Article  CAS  PubMed  Google Scholar 

  11. Alleyne CH, Barrow DL, Oyesiku NM (2002) Combined transsphenoidal and pterional craniotomy approach to giant pituitary tumors. Surg Neurol 57:380–390. https://doi.org/10.1016/s0090-3019(02)00705-x discussion 390.

    Article  PubMed  Google Scholar 

  12. Cottier J-P, Destrieux C, Brunereau L et al (2000) Cavernous sinus invasion by pituitary adenoma: MR imaging. Radiology 215:463–469. https://doi.org/10.1148/radiology.215.2.r00ap18463

    Article  CAS  PubMed  Google Scholar 

  13. Ahmadi J, North C, Segall H et al (1986) Cavernous sinus invasion by pituitary adenomas. Am J Roentgenol 146:257–262. https://doi.org/10.2214/ajr.146.2.257

    Article  CAS  Google Scholar 

  14. Scotti G, Yu C, Dillon W et al (1988) MR imaging of cavernous sinus involvement by pituitary adenomas. Am J Roentgenol 151:799–806. https://doi.org/10.2214/ajr.151.4.799

    Article  CAS  Google Scholar 

  15. Chen X, Dai J, Ai L et al (2011) Clival invasion on multi-detector CT in 390 pituitary macroadenomas: correlation with sex, subtype and rates of operative complication and recurrence. Am J Neuroradiol 32:785–789. https://doi.org/10.3174/ajnr.A2364

    Article  CAS  PubMed  Google Scholar 

  16. Prete A, Corsello SM, Salvatori R (2017) Current best practice in the management of patients after pituitary surgery. Ther Adv Endocrinol Metab 8:33–48. https://doi.org/10.1177/2042018816687240

    Article  PubMed  PubMed Central  Google Scholar 

  17. Cho SS, Lee JYK (2019) Intraoperative fluorescent visualization of pituitary adenomas. Neurosurg Clin N Am 30:401–412. https://doi.org/10.1016/j.nec.2019.05.002

    Article  PubMed  Google Scholar 

  18. Lakomkin N, Hadjipanayis CG (2019) The use of spectroscopy handheld tools in brain tumor surgery: current evidence and techniques. Front Surg 6:30. https://doi.org/10.3389/fsurg.2019.00030

    Article  PubMed  PubMed Central  Google Scholar 

  19. Chang SW, Donoho DA, Zada G (2019) Use of optical fluorescence agents during surgery for pituitary adenomas: current state of the field. J Neurooncol 141:585–593. https://doi.org/10.1007/s11060-018-03062-2

    Article  PubMed  Google Scholar 

  20. Sheehan J, Lee C-C, Bodach ME et al (2016) Congress of neurological surgeons systematic review and evidence-based guideline for the management of patients with residual or recurrent nonfunctioning pituitary adenomas. Neurosurgery 79:E539–E540. https://doi.org/10.1227/NEU.0000000000001385

    Article  PubMed  Google Scholar 

  21. Berkmann S, Schlaffer S, Nimsky C et al (2014) Intraoperative high-field MRI for transsphenoidal reoperations of nonfunctioning pituitary adenoma. J Neurosurg 121:1166–1175. https://doi.org/10.3171/2014.6.JNS131994

    Article  PubMed  Google Scholar 

  22. Lakomkin N, Hadjipanayis CG (2018) Fluorescence-guided surgery for high-grade gliomas. J Surg Oncol 118:356–361. https://doi.org/10.1002/jso.25154

    Article  PubMed  Google Scholar 

  23. Tonn J-C, Stummer W (2008) Fluorescence-guided resection of malignant gliomas using 5-aminolevulinic acid: practical use, risks, and pitfalls. Clin Neurosurg 55:20–26

    PubMed  Google Scholar 

  24. Ferraro N, Barbarite E, Albert TR et al (2016) The role of 5-aminolevulinic acid in brain tumor surgery: a systematic review. Neurosurg Rev 39:545–555. https://doi.org/10.1007/s10143-015-0695-2

    Article  PubMed  Google Scholar 

  25. Hadjipanayis CG, Stummer W, Sheehan JP (2019) 5-ALA fluorescence-guided surgery of CNS tumors. J Neurooncol 141:477–478. https://doi.org/10.1007/s11060-019-03109-y

    Article  PubMed  Google Scholar 

  26. Stummer W, Pichlmeier U, Meinel T et al (2006) Fluorescence-guided surgery with 5-aminolevulinic acid for resection of malignant glioma: a randomised controlled multicentre phase III trial. Lancet Oncol 7:392–401. https://doi.org/10.1016/S1470-2045(06)70665-9

    Article  CAS  PubMed  Google Scholar 

  27. Moody ED, Viskari PJ, Colyer CL (1999) Non-covalent labeling of human serum albumin with indocyanine green: a study by capillary electrophoresis with diode laser-induced fluorescence detection. J Chromatogr B 729:55–64. https://doi.org/10.1016/s0378-4347(99)00121-8

    Article  CAS  Google Scholar 

  28. Cho SS, Salinas R, Lee JYK (2019) Indocyanine-green for fluorescence-guided surgery of brain tumors: evidence, techniques, and practical experience. Front Surg.https://doi.org/10.3389/fsurg.2019.00011

    Article  PubMed  PubMed Central  Google Scholar 

  29. Fang J, Nakamura H, Maeda H (2011) The EPR effect: unique features of tumor blood vessels for drug delivery, factors involved, and limitations and augmentation of the effect. Adv Drug Deliv Rev 63:136–151. https://doi.org/10.1016/j.addr.2010.04.009

    Article  CAS  PubMed  Google Scholar 

  30. Onda N, Kimura M, Yoshida T, Shibutani M (2016) Preferential tumor cellular uptake and retention of indocyanine green for in vivo tumor imaging. Int J Cancer 139:673–682. https://doi.org/10.1002/ijc.30102

    Article  CAS  PubMed  Google Scholar 

  31. Predina JD, Newton AD, Connolly C et al (2018) Identification of a folate receptor-targeted near-infrared molecular contrast agent to localize pulmonary adenocarcinomas. Mol Ther 26:390–403. https://doi.org/10.1016/j.ymthe.2017.10.016

    Article  CAS  PubMed  Google Scholar 

  32. Xing L, Xu Y, Sun K et al (2018) Identification of a peptide for folate receptor alpha by phage display and its tumor targeting activity in ovary cancer xenograft. Sci Rep 8:1–13. https://doi.org/10.1038/s41598-018-26683-z

    Article  CAS  Google Scholar 

  33. Evans C-O, Reddy P, Brat DJ et al (2003) Differential expression of folate receptor in pituitary adenomas. Cancer Res 63:4218–4224

    CAS  PubMed  Google Scholar 

  34. Lee M, Pellegata NS (2013) Folate receptor-mediated drug targeting: a possible strategy for nonfunctioning pituitary adenomas? Endocrinology 154:1387–1389. https://doi.org/10.1210/en.2013-1182

    Article  CAS  PubMed  Google Scholar 

  35. Falco J, Cavallo C, Vetrano IG et al (2019) Fluorescein application in cranial and spinal tumors enhancing at preoperative MRI and operated with a dedicated filter on the surgical microscope: preliminary results in 279 patients enrolled in the FLUOCERTUM prospective study. Front Surg.https://doi.org/10.3389/fsurg.2019.00049

    Article  PubMed  PubMed Central  Google Scholar 

  36. Cavallo C, De Laurentis C, Vetrano IG et al (2018) The utilization of fluorescein in brain tumor surgery: a systematic review. J Neurosurg Sci 62:690–703. https://doi.org/10.23736/S0390-5616.18.04480-6

    Article  PubMed  Google Scholar 

  37. Nemes A, Fortmann T, Poeschke S et al (2016) 5-ALA fluorescence in native pituitary adenoma cell lines: resection control and basis for photodynamic therapy (PDT)? PLoS ONE 11:e0161364. https://doi.org/10.1371/journal.pone.0161364

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Neumann LM, Beseoglu K, Slotty PJ et al (2016) Efficacy of 5-aminolevulinic acid based photodynamic therapy in pituitary adenomas-experimental study on rat and human cell cultures. Photodiagnosis Photodyn Ther 14:77–83. https://doi.org/10.1016/j.pdpdt.2016.02.006

    Article  CAS  PubMed  Google Scholar 

  39. Marbacher S, Klinger E, Schwyzer L et al (2014) Use of fluorescence to guide resection or biopsy of primary brain tumors and brain metastases. Neurosurg Focus 36:E10. https://doi.org/10.3171/2013.12.FOCUS13464

    Article  PubMed  Google Scholar 

  40. Eljamel MS, Leese G, Moseley H (2009) Intraoperative optical identification of pituitary adenomas. J Neurooncol 92:417–421. https://doi.org/10.1007/s11060-009-9820-9

    Article  PubMed  Google Scholar 

  41. Lee JYK, Cho SS, Zeh R et al (2018) Folate receptor overexpression can be visualized in real time during pituitary adenoma endoscopic transsphenoidal surgery with near-infrared imaging. J Neurosurg 129:390–403. https://doi.org/10.3171/2017.2.JNS163191

    Article  CAS  PubMed  Google Scholar 

  42. Cho SS, Jeon J, Buch L et al (2018) Intraoperative near-infrared imaging with receptor-specific versus passive delivery of fluorescent agents in pituitary adenomas. J Neurosurg.https://doi.org/10.3171/2018.7.JNS181642

    Article  PubMed  Google Scholar 

  43. Cho SS, Zeh R, Pierce JT et al (2019) Folate receptor near-infrared optical imaging provides sensitive and specific intraoperative visualization of nonfunctional pituitary adenomas. Oper Neurosurg 16:59–70. https://doi.org/10.1093/ons/opy034

    Article  Google Scholar 

  44. Romano-Feinholz S, Alcocer-Barradas V, Benítez-Gasca A et al (2019) Hybrid fluorescein-guided surgery for pituitary adenoma resection: a pilot study. J Neurosurg.https://doi.org/10.3171/2019.1.JNS181512

    Article  PubMed  Google Scholar 

  45. Amano K, Aihara Y, Tsuzuki S et al (2019) Application of indocyanine green fluorescence endoscopic system in transsphenoidal surgery for pituitary tumors. Acta Neurochir (Wien) 161:695–706. https://doi.org/10.1007/s00701-018-03778-0

    Article  Google Scholar 

  46. Sandow N, Klene W, Elbelt U et al (2015) Intraoperative indocyanine green videoangiography for identification of pituitary adenomas using a microscopic transsphenoidal approach. Pituitary 18:613–620. https://doi.org/10.1007/s11102-014-0620-7

    Article  CAS  PubMed  Google Scholar 

  47. Litvack ZN, Zada G, Laws ER (2012) Indocyanine green fluorescence endoscopy for visual differentiation of pituitary tumor from surrounding structures: Clinical article. J Neurosurg 116:935–941. https://doi.org/10.3171/2012.1.JNS11601

    Article  PubMed  Google Scholar 

  48. Verstegen MJT, Tummers QRJG, Schutte PJ et al (2016) Intraoperative identification of a normal pituitary gland and an adenoma using near-infrared fluorescence imaging and low-dose indocyanine green. Oper Neurosurg 12:260–268. https://doi.org/10.1227/NEU.0000000000001328

    Article  Google Scholar 

  49. Hide T, Yano S, Shinojima N, Kuratsu J (2015) Usefulness of the indocyanine green fluorescence endoscope in endonasal transsphenoidal surgery. J Neurosurg 122:1185–1192. https://doi.org/10.3171/2014.9.JNS14599

    Article  PubMed  Google Scholar 

  50. Jeon JW, Cho SS, Nag S et al (2019) Near-infrared optical contrast of skull base tumors during endoscopic endonasal surgery. Oper Neurosurg 17:32–42. https://doi.org/10.1093/ons/opy213

    Article  Google Scholar 

  51. Belykh E, Martirosyan NL, Yagmurlu K et al (2016) Intraoperative fluorescence imaging for personalized brain tumor resection: current state and future directions. Front Surg 3:55. https://doi.org/10.3389/fsurg.2016.00055

    Article  PubMed  PubMed Central  Google Scholar 

  52. Valdés PA, Leblond F, Kim A et al (2011) Quantitative fluorescence in intracranial tumor: implications for ALA-induced PpIX as an intraoperative biomarker. J Neurosurg 115:11. https://doi.org/10.3171/2011.2.JNS101451

    Article  PubMed  PubMed Central  Google Scholar 

  53. Fisher RE, Siegel BA, Edell SL et al (2008) Exploratory study of 99mTc-EC20 imaging for identifying patients with folate receptor-positive solid tumors. J Nucl Med Off Publ Soc Nucl Med 49:899–906. https://doi.org/10.2967/jnumed.107.049478

    Article  Google Scholar 

  54. Baiocchi GL, Diana M, Boni L (2018) Indocyanine green-based fluorescence imaging in visceral and hepatobiliary and pancreatic surgery: state of the art and future directions. World J Gastroenterol 24:2921–2930. https://doi.org/10.3748/wjg.v24.i27.2921

    Article  PubMed  PubMed Central  Google Scholar 

  55. Cho SS, Zeh R, Pierce JT et al (2018) Comparison of near-infrared imaging camera systems for intracranial tumor detection. Mol Imaging Biol 20:213–220. https://doi.org/10.1007/s11307-017-1107-5

    Article  CAS  PubMed  Google Scholar 

  56. DSouza AV, Lin H, Henderson ER et al (2016) Review of fluorescence guided surgery systems: identification of key performance capabilities beyond indocyanine green imaging. J Biomed Opt 21:80901. https://doi.org/10.1117/1.JBO.21.8.080901

    Article  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Constantinos G. Hadjipanayis.

Ethics declarations

Conflict of interest

Constantinos Hadjipanayis is a consultant for NXDC and Synaptive Medical Inc. He will receive royalties from NXDC. He has also received speaker fees by Carl Zeiss and Leica.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lakomkin, N., Van Gompel, J.J., Post, K.D. et al. Fluorescence guided surgery for pituitary adenomas. J Neurooncol 151, 403–413 (2021). https://doi.org/10.1007/s11060-020-03420-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11060-020-03420-z

Keywords

Navigation